EXPRESSION OF GENETIC LOCI IN THE PERIPHERAL BLOOD MONONUCLEAR FRACTION FROM PATIENTS WITH PROSTATE CANCER

The early diagnosis and radical treatment of aggressive prostate cancers (PC) is an effective way of improving survival and quality of life in patients. To develop mini-invasive tests is one of the ways of solving the problem. The cells of a peripheral blood mononuclear fraction in the expression patterns of their genetic loci reflect the presence or absence of cancers, including information on therapeutic effectiveness. RT-PRC was used to study the relative expression of 15 genetic loci in a chromosome and one locus of mitochondrial DNA in the cells of the peripheral blood mononuclear fraction in patients with PC or benign prostate hyperplasia and in healthy men. The genetic locus patterns whose change may be of informative value for differential diagnosis in patients with different stages of PC were revealed. The authors studied the relationship and showed the prognostic role and non-relationship of the altered transcriptional activity of loci in the TP53, GSTP1, and IL10 genes in PC to the changes in prostate-specific antigen the level with 90 % specificity and 93 % specificity.

1. Jemal A., Siegel R., Xu J. et al. Cancer statistics. CA Cancer J Clin 2010;0(5):277−300.

2. Stamey T., Johnstone I., McNeal J. et al. Preoperative serum prostate specific antigen levels between 2 and 22 ng/ml correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng/ml. J Urol 2002;167:103−11.

3. Moreno J., Croce C., Fischer R. et al. Detection of hematogenous micrometastasis in patients with prostate cancer. Cancer Res 1992;52(21):6110−2.

4. Showe M., Vachani A., Kossenkov A.V. et al. Gene expression profiles in peripheral blood mononuclear cells can distinguish patients with non–small cell lung cancer from patients with nonmalignant lung disease. Cancer Res 2009;69(24):9202−10.

5. Komatsu N., Matsueda S., Tashiro K. et al. Gene expression profiles in peripheral blood as a biomarker in cancer patients receiving peptide vaccination. Cancer 2012; 118(12): 3208−21.

6. Novelli G., Ciccacci C., Borgiani P. et al. Genetic tests and genomic biomarkers: regulation, qualification and validation. Clin Cases Miner Bone Metab 2008;5(2):149−54.

7. Perambakam S., Srivastava R., Peace D.J. et al. Distinct cytokine patterns exist in peripheral blood mononuclear cell cultures of patients with prostate cancer. Clin Immunol 2005; 117(1):94−9.

8. Водолажский Д.И., Тимошкина Н.Н. Молекулярно-генетические маркеры рака предстательной железы. Вестник Южного научного центра 2009;5 (1):36−52.

9. Berteau P., Dumas F., Gala J.-L. et al. Molecular detection of circulating prostate cells in cancer II: comparison of prostate epithelial cells isolation procedures. Clin Chemistry 1998;44(8):1750−3.

10. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156−9.

11. Le Corre L., Fustier P.,Chalabi N. et al. Effects of resveratrol on the expression of a panel of genes interacting with the BRCA1 oncosuppressor in human breast cell lines. Clin Chim Acta 2004;344(1−2):115−21.

12. Armed Forces Institute of Pathology. Amplification of mitochondrial DNA 2005. Version 6.0.

13. Livak K., Schmittgen T. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001;25(4): 402−8.

14. Ratcliffe P. From erythropoietin to oxygen: hypoxia-inducible factor hydroxylases and the hypoxia signal pathway. Blood Purif 2002;20(5):445−50.

15. Gilmore T. Introduction to NF-κB: players, pathways, perspectives. Oncogene 2006;25(51):6680−804.

16. Locksley R.M., Killeen N., Lenardo M.J. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 2001; 104(4):487−501.

17. Kim J., Dang C. Cancer's molecular sweet tooth and the Warburg effect. Cancer Res 2006;66(18):8927−30.

18. Read A., Strachan T. Human molecular genetics 2. New York: Wiley; 1999. ISBN 0-471-33061-2. Chapter 18: Cancer Genetics.

19. Новик А.А., Камилова Т.А., Цыган В.Н. Введение в молекулярную биологию канцерогенеза. М.: ГЭОТАР-МЕД 2000:222 с.

20. Pollack A., Cowen D., Troncoso P. et al. Molecular markers of outcome after radiotherapy in patients with prostate carcinoma Ki-67, bcl-2, bax, and bcl-x. Cancer 2003;97(7):1630−8.

21. Алексеева М.Л., Щедрина Р.Н., Фанченко Н.Д. и др. Онкомаркеры, их характеристика и некоторые аспекты клинико-диагностического использования (обзор литературы). Проблемы репродукции 2005;3:65−78.